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微小RNA-26b-5p通过靶向S100A7调控人肝内胆管癌的细胞增殖、侵袭和转移。

MicroRNA-26b-5p regulates cell proliferation, invasion and metastasis in human intrahepatic cholangiocarcinoma by targeting S100A7.

作者信息

Fan Fei, Lu Jiongjiong, Yu Wenlong, Zhang Yongjie, Xu Suqian, Pang Leilei, Zhu Bin

机构信息

Department of Special Treatment, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, P.R. China.

Department of Biliary Surgery II, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, P.R. China.

出版信息

Oncol Lett. 2018 Jan;15(1):386-392. doi: 10.3892/ol.2017.7331. Epub 2017 Nov 2.

Abstract

The present study aimed to investigate the effects of microRNA expression in intrahepatic cholangiocarcinoma (ICC). It was identified that the expression of microRNA-26b-5p (miR-26b-5p) was downregulated in ICC tissues compared with matched adjacent non-tumor tissues. Furthermore, miR-26b-5p expression was downregulated in metastatic ICC tumor tissues and invasive ICC cell line subpopulations compared with non-metastatic tumor tissue and the parental ICC cells. studies demonstrated that transfection with an miR-26b-5p mimic inhibited the proliferation, migration and invasion of RBE and HCCC-9810 cells, whereas an miR-26b-5p inhibitor promoted these abilities. S100 calcium-binding protein A7 (S100A7) was predicted as a direct target of miR-26b-5p. Transfection with an miR-26b-5p mimic decreased S100A7 expression, whereas an miR-26b-5p inhibitor increased S100A7 expression. The result of a dual luciferase reporter assay also indicated this interaction. S100A7 was therefore confirmed as a direct target of miR-26b-5p in ICC. The knockdown of S100A7 abrogated the effect of miR-26b-5p on cell migration in RBE and HCCC-9810 cells. In conclusion, the present study demonstrated that miR-26b-5p suppresses the proliferation, migration and invasion of ICC cells by suppressing S100A7.

摘要

本研究旨在探讨微小RNA表达在肝内胆管癌(ICC)中的作用。研究发现,与配对的癌旁非肿瘤组织相比,微小RNA-26b-5p(miR-26b-5p)在ICC组织中的表达下调。此外,与非转移性肿瘤组织和原代ICC细胞相比,miR-26b-5p在转移性ICC肿瘤组织和侵袭性ICC细胞系亚群中的表达也下调。研究表明,转染miR-26b-5p模拟物可抑制RBE和HCCC-9810细胞的增殖、迁移和侵袭,而miR-26b-5p抑制剂则促进这些能力。S100钙结合蛋白A7(S100A7)被预测为miR-26b-5p的直接靶标。转染miR-26b-5p模拟物可降低S100A7的表达,而miR-26b-5p抑制剂则增加S100A7的表达。双荧光素酶报告基因检测结果也表明了这种相互作用。因此,S100A7被确认为ICC中miR-26b-5p的直接靶标。敲低S100A7可消除miR-26b-5p对RBE和HCCC-9810细胞迁移的影响。总之,本研究表明miR-26b-5p通过抑制S100A7来抑制ICC细胞的增殖、迁移和侵袭。

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